The mechanism of hepatic uptake of organic anions such as bilirubin and heme is unknown. This lack of information hampers the diagnosis and treatment of hyperbilirubinemia associated with Kernicterus. A serum protein, termed histidine-rich glycoprotein (HRG), present in human, rat and rabbit sera binds these organic anions with high affinity. This suggests that HRG may have an important role in the transport and tissue disposition of these anions. This protein has been isolated from human serum and its physiochemical properties are under study. The interaction of HRG with a variety of organic anions including bilirubin, heme, dyes, bromosulfophthalein, and steroids is being evaluated. This information will be used in investigation of the biological function of this protein. In particular, the effects of HRG on the uptake of organic anions by isolated rat liver parenchymal cells will be examined.